Distinctive Network Topology of Phase-Separated Proteins in Human Interactome |
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| Institution: | 1. Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;2. Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;3. Beijing Advanced Innovation Centre for Genomics, Peking-Tsinghua Centre for Life Sciences, Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China;1. Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany;2. Max Planck Tandem Group in Computational Biophysics, University of Los Andes, Cra. 1 #18a-12, 111711 Bogotá, Colombia;3. Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany;4. International Max Planck Research School for Living Matter, Otto-Hahn-Straße 11, 44227 Dortmund, Germany;5. University of Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany;6. Max Planck School Matter to Life, Jahnstrasse 29, 69120 Heidelberg, Germany;7. Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany;8. Interdisciplinary Center for Scientific Computing, Heidelberg University, INF 205, 69120 Heidelberg, Germany;1. Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;2. Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas, USA;2. Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado, USA;3. Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, Mississippi, USA;4. Department of Chemistry, Mississippi State University, Mississippi State, Mississippi, USA;5. Department of Physics, University of Colorado Boulder, Boulder, Colorado, USA;6. BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA;1. IEO, Istituto Europeo di Oncologia IRCCS, Via Ripamonti 435, 20141, Milan, Italy;2. Università degli Studi di Milano, Dipartimento di Oncologia ed Emato-oncologia, Via Santa Sofia 9/1, 20122, Milan, Italy;3. University of Texas, Department of Biomedical Engineering, 107 W. Dean Keeton St., C0800, Austin, TX, USA;1. Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, 6525 GA Nijmegen, the Netherlands;2. Max Planck Institute (MPI) for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany;3. Dewpoint Therapeutics GmbH, c/o Max Planck Institute (MPI) for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany;4. Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, the Netherlands |
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| Abstract: | Liquid-liquid phase separation (LLPS) is an important mechanism that mediates the formation of biomolecular condensates. Despite the immense interest in LLPS, phase-separated proteins verified by experiments are still limited, and identification of phase-separated proteins at proteome-scale is a challenging task. Multivalent interaction among macromolecules is the driving force of LLPS, which suggests that phase-separated proteins may harbor distinct biological characteristics in protein–protein interactions (PPIs). In this study, we constructed an integrated human PPI network (HPIN) and mapped phase-separated proteins into it. Analysis of the network parameters revealed differences of network topology between phase-separated proteins and others. The results further suggested the efficiency when applying topological similarities in distinguishing components of MLOs. Furthermore, we found that affinity purification mass spectrometry (AP-MS) detects PPIs more effectively than yeast-two hybrid system (Y2H) in phase separation-driven condensates. Our work provides the first global view of the distinct network topology of phase-separated proteins in human interactome, suggesting incorporation of PPI network for LLPS prediction in further studies. |
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| Keywords: | phase separation protein–protein interaction membrane-less organelle network clustering node embedding |
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